This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Utama, F. E. Articles by Rui, H. Search for Related Content PubMed PubMed Citation Articles by Utama, F. E. Articles by Rui, H.

Insensitivity of Human Prolactin Receptors to Nonhuman Prolactins: Relevance for Experimental Modeling of Prolactin Receptor-Expressing Human Cells

Department of Cancer Biology (F.E.U., T.H.T., A.R., M.J.L., H.R.), Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107; and National Hormone and Peptide Program (A.F.P.), Harbor-UCLA Medical Center, Torrance, California 90509

Address all correspondence and requests for reprints to: Hallgeir Rui, Department of Cancer Biology, Thomas Jefferson University, 233 South 10th Street, BLSB 330, Philadelphia, Pennsylvania 19107. E-mail: hallgeir.rui{at}jefferson.edu.

Prolactin (PRL) receptors are expressed in a broad range of human cell types and in a majority of human breast and prostate cancers. Experimentally, normal and malignant human cells are typically cultured in vitro in media containing bovine PRL (bPRL) from fetal bovine serum or as xenotransplants in vivo in the presence of murine PRL (mPRL). The biological efficacy of bPRL toward hPRL receptors (hPRLR) is controversial, and hPRLR are insensitive to mPRL, but the mechanism is not known. To clarify limitations of current in vitro and in vivo experimental model systems for studies of hPRLR-expressing cells, we tested human and relevant subprimate prolactins in multiple hPRLR bioassays. bPRL and ovine PRL were 10-fold less potent hPRLR agonists than hPRL, although maximal responses at high ligand concentrations (efficacies) equaled that of hPRL. mPRL and rat PRL had greater than 50-fold lower potencies toward hPRLR than hPRL and had 50% reduced efficacies. In fact, mPRL and rat PRL were less effective hPRLR agonists than murine GH. Unexpectedly, mPRL was an effective competitive inhibitor of hPRL binding to hPRLR with an inhibitory constant of 1.3 nM and showed partial antagonist activity, suggesting reduced site-2 binding. Collectively, low bioactivities of bPRL and mPRL toward hPRLR suggest that existing laboratory cancer cell lines grown in 10% bovine serum-supplemented media or in mice are selected for growth under lactogen-depleted conditions. The biology and drug responsiveness of existing human cell lines may therefore not be representative of clinical cancers that are sensitive to circulating PRL.